Aryl hydrocarbon receptor activation modulates intestinal intraepithelial lymphocytes and protects against ischemia/reperfusion injury in the murine small intestine

The pathogenesis of intestinal ischemia/reperfusion (I/R) is associated with dysregulation of the intestinal immune system. The aryl hydrocarbon receptor (AhR), a receptor expressed in gamma-delta () intraepithelial lymphocytes (IELs), is thought to regulate inflammation in the bowel. IELs are a key immunologic compartment with a capacity to modulate immune responses. In the present study, the function of the AhR in IELs in a mouse model of intestinal I/R injury was investigated to determine whether the AhR attenuates intestinal injury induced by intestinal I/R. Mice were assigned to three groups: sham, I/R and I/R+6-formylindolo(3,2-b)carbazole (FICZ). The sham group received no ischemia treatment, whereas the I/R and I/R+FICZ groups underwent upper mesenteric vessel ischemia for 30 min. The I/R group was injected intraperitoneally with 0.3 ml saline and the I/R+FICZ group was administered 1 mu g of FICZ before a subsequent 6 h reperfusion. Then, the mice were sacrificed and the entire small intestinal tissues were collected for histologic examination. The phenotype and apoptosis of IELs and activation of CD4(+) and CD8(+) IELs were examined using flow cytometry. The cytokine mRNA and anti-apoptosis gene expression in IELs were measured by qPCR. FICZ increased the IEL population and anti-apoptosis genes in the IELs. FICZ reduced the percentage of activated CD4(+) and CD8(+) subpopulations and the expression of pro-inflammatory mediator genes in IELs. FICZ inhibited inflammation in the gastrointestinal tract of mice with I/R injury. These results suggest that the AhR plays an important role in protecting the small intestine from I/R and increasing the IEL population by decreasing apoptosis of IELs.